Neurosyphilis

Neurosyphilis is invasion of the central nervous system by Treponema pallidum, which can occur at any stage of syphilis. Early forms (syphilitic meningitis, meningovascular syphilis) appear within months to a few years; late forms (general paresis, tabes dorsalis) appear after 5 to 30 years.

• HIV infection increases the risk and speeds progression.
• Asymptomatic neurosyphilis is shown by CSF abnormalities alone.

Syphilitic meningitis: headache, neck stiffness, cranial nerve palsies (II, VII, VIII), seizures. Meningovascular: stroke syndromes in young adults. General paresis: progressive dementia, personality change, psychosis, tremor, dysarthria. Tabes dorsalis: lightning pains, ataxia, loss of position sense, absent reflexes, bladder dysfunction, Argyll Robertson pupils (accommodate but do not react), Charcot joints.

• Differential diagnosis: HIV dementia, tuberculous and cryptococcal meningitis, Alzheimer disease, vitamin B12 deficiency, multiple sclerosis, stroke from other causes, psychiatric disease, diabetic neuropathy, CNS lymphoma, Lyme disease.
• Complications: dementia, blindness, deafness, stroke, paraplegia, bladder dysfunction, optic atrophy, death.

Serology plus CSF.

• Serum treponemal and non treponemal tests; HIV test and CD4.
• CSF: lymphocytic pleocytosis (over 5 cells/mm3, over 20 in HIV), raised protein (over 45 mg/dL), reactive CSF VDRL (specific, not sensitive), CSF treponemal test (sensitive); CSF PCR is inconsistent.
• MRI brain and spine, MRA for vasculitis; ophthalmology and audiology review.
• Test CSF in any syphilis patient with neurological, ocular or otic symptoms, tertiary signs, or treatment failure.

High dose intravenous penicillin penetrates CSF.

• Supportive: admission, seizure precautions, falls prevention, physiotherapy, bladder care, neuropsychiatric support, analgesia for lightning pains, counselling on partner notification (all partners within 90 days).
• Pharmacological: benzylpenicillin 18 to 24 million units daily IV (3 to 4 million units every 4 hours, or continuous infusion) for 10 to 14 days; alternative procaine benzylpenicillin 2.4 million units IM daily with probenecid 500 mg four times daily for 10 to 14 days; or ceftriaxone 2 g IV daily for 10 to 14 days. Many specialists follow with benzathine benzylpenicillin 2.4 million units IM weekly for 3 doses. Jarisch Herxheimer reaction: paracetamol 1 g, consider prednisolone 20 to 40 mg for 3 days in general paresis. Anticonvulsant: levetiracetam 500 mg twice daily. Lightning pains: gabapentin 300 mg at night titrated to 900 to 1800 mg daily in divided doses, or carbamazepine 200 mg twice daily. Antiretroviral therapy in HIV.
• Procedures: lumbar puncture; bladder catheterisation; orthopaedic care for Charcot joints.
• Special groups: pregnancy, IV penicillin (desensitise if allergic) with fetal assessment; HIV, give the full penicillin course and start antiretroviral therapy early; penicillin allergy, ceftriaxone or desensitisation; renal impairment, adjust doses.
• Red flags: acute stroke, seizures, rapid cognitive decline, visual loss, hearing loss, urinary retention, suicidal ideation.
• Follow-up: repeat CSF at 6 months and every 6 months until cell count is normal; retreat if cells have not fallen by 6 months or CSF VDRL has not fallen fourfold by 2 years; serum RPR at 3, 6, 12 and 24 months.